DESCRIPTION: Furin is a membrane-localized endoprotease that cleaves a number of biologically important molecules as part of their normal biosynthesis and processing. Cleavage takes place in the TGN and also in endosomes and at the cell surface. The applicant has invested a great deal of effort in analyzing the role of specific cytoplasmic domain residues in facilitating the endocytosis and TGN recycling of this important processing protease. The goals of this application are to: (1) use quantitative assays of furin trafficking and explore the effects of specific cytosolic tail mutations and phosphorylation/dephosphorylation on these steps; (2) characterize a tautomycin sensitive furin phosphatase that seems to play a role in early endosome export of the protein; and (3) characterize the role of actin binding protein-ABP-280 on furin cycling.